Investigating Direct Access to 2‐Oxospiro[4.5]decanones via 6π‐Electrocyclisation

Abstract

The 2-oxospiro[4.5]decan-1-one (or spiro-γ-lactone) structural motif is contained within a number of natural products, for example, the clerodane family of diterpenes. Methods to construct this structural motif are somewhat limited and usually involve multiple functional group interconversions. A novel synthetic approach to this system utilising 6π-electro-The 2-oxospiro[4.5]decan-1-one (1) structural motif exists within a number of natural product groups [e.g. canangone (2), [1] teusalvin A (3) [2] ], of which the clerodanes [3] (i.e. 3) are a major contributor (Figure 1). Considering the usual mode of 2-oxospiro[4.5]decan-1-one construction is to assemble the lactone portion at a later stage, [4][5][6][7][8][9][10][11][12][13][14] which often involves multiple steps, we contemplated the approach of initial γ-lactone inclusion (i.e. construction of the six-membered ring at the later stage). Although this approach presents limitations it does open additional avenues for constructing the 2-oxospiro[4.5]-decan-1-one structural motif (1) directly. In this regard we are only aware of two examples that fit this criterion. [15][16] Of note is the Diels-Alder approach reported by Jung et [a] al. [15] in which allenic lactones 5 and 7 were treated with diene 6 affording the 2-oxospiro[4.5]decan-1-ones 4 and 8 (Scheme 1). Scheme 1. Diels-Alder approach to the 2-oxospiro[4.5]decan-1-one structural motif.With these examples in mind, it seemed reasonable that a 6π-electrocyclisation approach to the six-membered ring (i.e. 2-oxospiro[4.5]decan-1-ones of type 4 and 8) was worthy of investigation. For example, the lactone trienes 9 and 10, via thermal or photochemical conditions, could be transformed into cyclised adducts 11 (12) and 13 (14), which then have the potential to undergo [1,5]-hydrogen shifts, affording the dienes 15 (16) and 17 (18). An additional advantage to this approach would be the relative stereocontrol of the products as described by the Woodward-Hoffmann principles [17][18][19] (Scheme 2). To test the viability of this method a suite of compounds of type 9 were synthesised in good to excellent yields by Sonogashira coupling [20][21][22] of the corresponding alkyne, followed by partial hydrogenation to give the cis-alkenes 28-31, 38-40 (Scheme 3), as well as 45 and 46 (Scheme 4).The partial hydrogenation of these systems was at times capricious, however, neither diimide or boron mediated reduction gave satisfactory results. Furthermore, all attempts to reduce 27 to 31 failed. Though direct synthesis of the aromatic dienes and trienes through Stille coupling is an appealing route, it was found that the triflate 23 did not react with vinyl stannanes at temperatures low enough to

Chromatography with silver nitrate: part 2

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New and Scalable Access to Karrikin (KAR1) and Evaluation of Its Potential Application on Corn Germination

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Stereocontrolled Synthesis of the cis‐Hydroxydecalin System: Towards Biologically Active 19‐nor‐Clerodanes

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